Compass Therapeutics shed half its stock price this morning as investors digested its bispecific antibody’s failure to hit an overall survival (OS) endpoint in a phase 2/3 study.
The Boston-based biotech was evaluating the DLL4xVEGF-A bispecific antibody, called tovecimig, along with chemotherapy against chemotherapy alone as a second-line treatment for 168 adults with unresectable advanced, metastatic or recurrent biliary tract cancer.
Compass already revealed a year ago that the tovecimig-chemo combo met the study’s primary endpoint of demonstrating an overall response rate (ORR) of 17.1% versus 5.3% for the chemotherapy monotherapy cohort.
This morning’s readout saw the biotech disclose how the study’s two secondary endpoints had fared. Tovecimig was tied to a 4.7-month media progression-free survival versus 2.6 months for the control group, which Compass hailed as a statistically significant improvement.
But the readout for OS was less welcome, with the 8.9 months of the tovecimig group actually coming in lower than the 9.4 months for patients who received chemotherapy only.
Compass blamed this miss on “high crossover from the control arm,” noting that 31 of the 57 patients who started in the control arm were transferred to the tovecimig group. The company said it had used a so-called rank-preserving structural failure time (RPSFT) OS analysis that is designed to take account of these sorts of crossover situations.
However, the RPSFT analysis “depends on certain assumptions that were not met in this study and thus its results here are largely uninterpretable,” the biotech said.
Despite the mixed results, Compass is sticking to its plans to discuss the data with the FDA ahead of a planned approval filing.
“The remarkable 56% reduction in the risk of disease progression is unprecedented in this patient population without an actionable mutation in their tumor,” Compass CEO Thomas Schuetz, M.D., Ph.D., said in an April 27 release.
“It is also notable that the 31 crossover patients survived a median of 12.8 months, similar to the median OS seen in front-line studies in this setting,” Schuetz added. “Including crossover, 85% of patients in the study received tovecimig in combination with paclitaxel and the pooled median OS for all patients in the study was 8.9 months, which is also substantially longer than chemotherapy benchmarks of approximately six months.”
Investors didn’t seem reassured, sending Compass’ stock down 53% to $2.40 by 10.30 am ET on Monday morning from a Friday closing price of $5.63.
William Blair analysts said the OS miss “will raise questions on the approvability of this dataset.”
“While we believe the totality of the data shows that tovecimig provides clinical benefit in this patient population, it will clearly be a review issue at the FDA,” they added in an April 27 note. “The next key update will be feedback from the company’s pre-BLA meeting, likely in mid-2026, with investor focus on support for a BLA filing and whether there is any commentary on accelerated versus full approval submissions.”